The proposed research has as a central focus the goal of contributing to a deeper insight into protein structure and the resultant function. However, the points of attack can logically be divided into five areas. 1. Development of novel approaches for the refinement of the crystal structures of biological macromolecules and the application of these methods as well as conventional ones to specific problems especially the structure of uninhibited and inhibited Staphylococcal nuclease. 2. Use of low-temperature crystallographic techniques, again using the carboxypeptidase A-gamma as the prime subject, in attempts to improve the quality of the overall structures, to examine the structures of the hydrating water at the protein surface and to directly determine the structures of enzyme-substrate and enzyme-intermediates complexes. 3. Characterization and structural studies of crystals isolated from crude pituitary extracts containing growth hormone and at least two peptide other components. 4. Design, synthesis and study of the structure and properties of simplified peptide models of the beta-barrel domain, a sub-unit of the overall tertiary structure in a number of different proteins of apparently otherwise diverse structure and function.